P909: POMALIDOMIDE, BORTEZOMIB, AND DEXAMETHASONE CHEMOTHERAPY FOR NEWLY DIAGNOSED MULTIPLE MYELOMA: POMACE PHASE II STUDY
Authors: Fen Saj, Yadav Nisha, Prasanth Ganesan, Smita Kayal, Rakhee Kar, Dhanapathi Halanaik, Biswajit Dubashi
Journal: HemaSphere (2023)

Topic: 14. Myeloma and other monoclonal gammopathies - Clinical Background: Bortezomib, lenalidomide, and dexamethasone induction chemotherapy (VRd), followed by autologous stem cell transplantation (ASCT), are the standard of care for patients with newly diagnosed multiple myeloma (NDMM). Pomalidomide is a third-generation immunomodulatory drug currently approved for relapsed-refractory multiple myeloma. Aims: This single-arm, open-label, phase 2 study was the prospective evaluation of the efficacy and safety of bortezomib, pomalidomide, and dexamethasone (VPd) induction for NDMM. The primary endpoint was to determine the rates of very good partial response or better (≥VGPR) after four courses of VPd. The secondary endpoints were the assessment of safety, progression-free survival (PFS), and overall survival (OS). Methods: Patients with newly diagnosed multiple myeloma, aged between 18-75 years, who were treatment naïve and had an Eastern Cooperative Group Performance Status (ECOG-PS) 2 or below were eligible (Fig No. 1). We included transplant-eligible and ineligible patients in the study. We used Fleming’s two-stage design for sample size calculation. Four courses of induction chemotherapy (each cycle of 4 weeks) of subcutaneous bortezomib 1.3mg/m2/day on days 1, 8, 15, and 22; oral pomalidomide on days 1 to 21 (2mg/day dose in cycle 1 and 4mg/day dose from cycle two onwards); and oral dexamethasone 40mg/day on days 1, 8, 15, 22 were given (VPd regimen). Complete response assessment was done at the end of four cycles, including serum protein electrophoresis, immunofixation, serum free light chain assay, bone marrow biopsy, and PET/CT scanning. Transplant-eligible patients proceeded for ASCT after 4-6 cycles, followed by maintenance. Transplant-ineligible patients continued the VPd regimen for nine cycles, followed by maintenance. Results: Thirty-four patients were included in the study, of which 31 completed all four cycles of induction. The median age was 52 years (32-72), and males were 17 (51%). Thirty (91%) patients had multiple myeloma, and three had multiple plasmacytomas with less than 10% bone marrow involvement. Nine (27%) had international staging system (ISS)-I, 9 (27%) had ISS-II, and 15 (46%) had ISS-III myeloma. Four patients had high-risk cytogenetic abnormalities by FISH. After four cycles of VPd induction, ten patients (32%) achieved stringent complete response (sCR), nine had CR (29%), eight (26%) had VGPR, and 4 (13%) had a partial response (PR). Fifteen (48%) had a complete metabolic response (CMR) on PET/CT. ASCT was performed on 11 patients. Pomalidomide did not interfere with stem cell harvest. Two patients developed serious adverse events (SAEs) resulting in death. Anemia (21%) was the most common hematological toxicity. Peripheral neuropathy (27%), fatigue (27%), and constipation (24%) were the most common non-hematological toxicities. Patients with ≥VGPR had significantly better 12-month PFS than those with PR. Patients with ≥VGPR and CMR on PET-CT had significantly better 12-month OS. Summary/Conclusion: Induction chemotherapy using bortezomib, pomalidomide, and dexamethasone is safe and efficacious in newly diagnosed multiple myeloma. Further Phase 3 studies with longer follow-ups are necessary to establish the superiority and survival benefit of the pomalidomide-based regimen for myeloma induction.Keywords: Multiple myeloma, Clinical trial, Induction chemotherapy